Considering endophenotypes, tested first in animals and then in humans, as potential targets for new treatments may enable us to circumvent the obstacles in pharmacological studies, represented by ethical concerns as well as issues with obtaining adequate sample sizes. Clinical trials could potentially aim to investigate the effects of a new compound, not on the rare SB directly, but on the related endophenotypes, measurable quantitatively, which would address the validity of assessing outcomes with low base rates in the general population, potentially avoiding false positives. This is now the case with the MATRICS and related programs aimed at cognition in schizophrenia.89 Moreover, measuring the same endophenotypes in unaffected relatives of cases will enhance the statistical power of such studies. Evaluation of new treatments for SB could be based on the involvement of identified cognitive and emotional processes, related to dysfunction of the orbitofrontal cortex in the pathophysiology of SB. Improving decision making and emotions, that is to say focused psychotherapeutic interventions, can be proposed to complement additional strategies. For example, it has been demonstrated that stimulation of the prefrontal cortex
